Skip to main content
Log in

Expression of transforming growth factor-β receptor type I and type II in rat ventral prostate and Dunning R3327 PAP adenocarcinoma in response to castration and oestrogen treatment

  • Original Paper
  • Published:
Urological Research Aims and scope Submit manuscript

Abstract

In the normal prostate, transforming growth factor-β1 (TGF-β1) inhibits epithelial cell growth and is associated with apoptosis. The role of TGF-β1 in prostate cancer remains, however, unclear. In this work, the expression of TGF-β receptor type I and II (TGFβ-RI and TGFβ-RII) in the Dunning R3327 PAP adenocarcinoma was studied, after castration and oestrogen treatment. Since castration induces apoptosis in the rat ventral prostate (VP) [21], but not in the Dunning R3327 PAP tumour [46], the TGF-β receptor levels in the tumour were compared to the receptor levels in the VP. Methods used were competitive reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. In the VP, TGFβ-RI and TGFβ-RII expressions were increased after castration, indicating a negative regulation of TGFβ receptors by androgens. In the Dunning tumour, TGFβ-RI and TGFβ-RII levels were elevated and only TGFβ-RI showed a clear-cut increase after castration. The receptors were located in epithelial and smooth muscle cells in the VP and mainly in epithelial cells in the Dunning tumour. In conclusion, the elevated TGFβ receptor levels and the diminished androgen regulation of TGFβ-RII in the tumour distinguish the Dunning R3327 PAP tumour from the normal prostate and need to be further elucidated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Arteaga CL, Tandon AK, Von Hoff DD, Osborne CK (1988) Transforming growth factor β: potential autocrine growth inhibitor of estrogen receptor-negative human breast cancer cells. Cancer Res 48:3898

    Google Scholar 

  • Bassing CH, Howe DJ, Segarini PR, Donahoe PK, Wang X-F (1994) A single heteromeric receptor complex is sufficient to mediate biological effects of transforming growth factor-β ligands. J Biol Chem 269:14861

    Google Scholar 

  • Celi FS, Zenilman ME, Shuldiner AR (1993) A rapid and versatile method to synthesize internal standards for competitive PCR. Nucleic Acids Res 21:1047

    Google Scholar 

  • Chen RH, Moses HL, Maruoka EM, Derynck R, Kawabata M (1995) Phosphorylation-dependent interaction of the cytoplasmic domains of the type I and type II transforming growth factor-β receptors. J Biol Chem 270:12235

    Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156

    Google Scholar 

  • Danielson PE, Forss-Petter S, Brow MA, Calavetta L, Douglass J, Milner RJ, Sutcliffe JG (1988) p1B15: a cDNA clone of the rat mRNA encoding cyclophilin. DNA 7:261

    Google Scholar 

  • Derynck R, Goeddel DV, Ullrich A, Gutterman JU, Williams RD, Bringman TS, Berger WH (1987) Synthesis of messenger RNAs for transforming growth factors α and β and the epidermal growth factor receptor by human tumors. Cancer Res 47:707

    Google Scholar 

  • English HF, Kyprianou N, Isaacs JT (1989) Relationship between DNA fragmentation and apoptosis in the programmed cell death in the rat prostate following castration. Prostate 15:233

    Google Scholar 

  • Filmus J, Zhao J, Buick RN (1992) Overexpression of H-ras oncogene induces resistance to the growth-inhibitory action of transforming growth factor β-1 (TGF-β1) and alters the number and type of TGF- β1 receptors in rat intestinal epithelial cell clones. Oncogene 7:521

    Google Scholar 

  • Franze'n P, ten Dijke P Ichijo H, Yamashita H, Schulz P, Heldin C-H, Miyazono K (1993) Cloning of a TGF-β type I receptor that forms a heteromeric complex with the TGF-β type II receptor. Cell 75:681

    Google Scholar 

  • Garrigue-Antar L, Munos-Antonia T, Antonia SJ, Gesmonde J, Vellucci VF, Reiss M (1995) Missense mutation of the transforming growth factor β type II receptor in human head and neck squamous carcinoma cells. Cancer Res 55:3982

    Google Scholar 

  • Geiser AG, Burmester JK, Webbink R, Roberts AB, Sporn MB (1992) Inhibition of growth by transforming growth factor-β following fusion of two nonresponsive human carcinoma cell lines. J Biol Chem 267:2588

    Google Scholar 

  • Haendler B, Hofer B (1990) Characterization of the human cyclophilin gene and of related processed pseudogenes. Eur J Biochem 190:477

    Google Scholar 

  • Ilio KY, Sensibar JA, Lee C (1995) Effect of TGF-β1, TGF-α and EGF on cell proliferation and cell death in rat ventral prostatic epithelial cells in culture. J Androl 16:482

    Google Scholar 

  • Ito M, Yasui W, Nakayama H, Yokozaki H, Ito H, Tahara E (1992) Reduced levels of transforming growth factor-β type I receptor in human gastric cancer. Jpn J Cancer Res 83:86

    Google Scholar 

  • Kalkhoven E, Roelen BAJ, de Winter JP, Mummery CL, van den Eijnden-van Raaij AIM, van der Saag PT, van der Burg B (1995) Resistance to transforming growth factor β and activin due to reduced receptor expression in human breast tumor cell lines. Cell Growth Differ 6:1151

    Google Scholar 

  • Kassen A, Sutkowski DM, Ahn H, Sensibar JA, Kozlowski JM, Lee C (1996) Stromal cells of the human prostate: initial isolation and characterization. Prostate 28:89

    Google Scholar 

  • Kim IY, Ahn H-J, Zelner DJ, Park L, Sensibar JA, Lee C (1996) Expression and localization of transforming growth factor-β receptors type I and type II in the rat ventral prostate during regression. Mol Endocrinol 10:107

    Google Scholar 

  • Kimchi A, Wang XF, Weinberg RA, Cheifetz S, Massague J (1988) Absence of TGF-β receptors and growth inhibitory responses in retinoblastoma cells. Science 240:196

    Google Scholar 

  • Kyprianou N, Isaacs JT (1988) Identification of a cellular receptor for transforming growth factor-β in rat ventral prostate and its negative regulation by androgens. Endocrinology 123:2124

    Google Scholar 

  • Kyprianou N, Isaacs JT (1989) Expression of transforming growth factor-β in the rat ventral prostate during castration induced programmed cell death. Mol Endocrinol 3:1515

    Google Scholar 

  • Kyprianou N, English HF, Issacs JT (1990) Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation. Cancer Res 50:3748

    Google Scholar 

  • Landström M, Bergh A, Tomic R, Damber J-E (1990) Estrogen treatment combined with castration inhibits tumor growth more effectively than castration alone in the Dunning R3327 rat prostatic adenocarcinoma. Prostate 17:57

    Google Scholar 

  • Landström M, Damber J-E, Berg A, Tomic R (1992) Dose/respouse study of the effects of oestrogens on tumor growth and morphology in Dunning R3327 prostatic adenocarcinoma. J Cancer Res Clin Oncol 118:30

    Google Scholar 

  • Lin HY, Wang X-F, Ng-Eaton E, Weinberg RA, Lodish HF (1992) Expression cloning of the TGF-β type II receptor, a functional transmembrane serine/threonine kinase. Cell 68:775

    Google Scholar 

  • Lindström P, Bergh A, Holm I, Damber J-E (1996) Expression of TGF-β1 in rat ventral prostate and Dunning R3327 PAP prostate tumor after castration and estrogen treatment. Prostate (in press)

  • Lopez-Casillas F, Cheifetz S, Doody J, Andres JL. Lane WS, Massague' J (1991) Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-β receptor system. Cell 54:659

    Google Scholar 

  • Markowitz S, Wang J, Myeroff L, Parsosns R, Sun L, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW, Vogelstein B, Brattain M, Willson JKW (1995) Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science 268:1336

    Google Scholar 

  • Martikainen P, Kyprianou N, Issacs JT (1990) Effect of transforming growth factor-β on proliferation and death of rat prostatic cells. Endocrinology 127:2963

    Google Scholar 

  • Massague J (1990) The transforming growth factor-β family. Annu Rev Cell Biol 6:597

    Google Scholar 

  • McKeehan WL, Adams PS (1988) Heparin-binding growth factor/ prostatatropin attenuates inhibition of rat prostate tumor epithelial cell growth by transforming growth factor type β. In Vitro Cell Dev Biol 24:243

    Google Scholar 

  • Mulder KM, Segarini PR, Morris SL, Ziman JM, Choi HG (1993) Role of receptor complexes in resistance or sensitivity to growth inhibition by TGFβ in intestinal epithelial cell clones. J Cell Physiol 154:162

    Google Scholar 

  • Park K, Kim S-J, Bang Y-J, Park J-G, Kim NK, Roberts A, Sporn MB (1994) Genetic changes in the transforming growth factor β (TGF-β) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-β. Proc Natl Acad Sci U S A 91:8772

    Google Scholar 

  • Steiner MS, Barrack ER (1990) Expression of transforming growth factors (TGFα and TGFβ) and epidermal growth factor (EGF) in normal and malignant rat prostate. J Urol 143:240A

    Google Scholar 

  • Steiner MS, Barrack ER (1992) Transforming growth factor-(31 overproduction in prostate cancer: effects of growth in vivo and in vitro. Mol Endocrinol 6:15

    Google Scholar 

  • Steiner MS, Zhou Z-Z, Tonb DC, Barrack ER (1994) Expression of transforming growth factor-β1 in prostate cancer. Endocrinology 13:2240

    Google Scholar 

  • Sun L, Wu G, Willson JKV, Zborowska E, Yang J, Rajkarunanayake I, Wang J, Gentry LE, Wang X-F, Brattain MG (1994) Expression of transforming growth factor β type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells. J Biol Chem 269:26449

    Google Scholar 

  • Taylor CR, Shi S-R, Chaiwun B, Young L, Imam SR, Cote RJ (1994) Strategies for improving the immunohistochemical staining of various intranuclear prognostic markers in formalinparaffin sections. Hum Pathol 25:263

    Google Scholar 

  • Thompson TC, Truong LD, Timme TL, Kadmon D, McCune BK, Flanders KC, Scardino PT, Park SH (1992) Transforming growth factor β as a biomarker for prostate cancer. J Cell Biochem 16H:54

    Google Scholar 

  • Truong LD, Kadmon D, McCune BK, Flanders KC, Scardino PT, Thompson TC (1993) Association of transforming growth factor β with prostate cancer: an immunohistochemical study. Hum Pathol 24:4

    Google Scholar 

  • Tsuchida K, Lewis KA, Mathews LS, Vale WW (1993) Molecular characterization of rat transforming growth factor-β type II receptor. Biochem Biophys Res Commun 191:790

    Google Scholar 

  • Wang J, Sun LZ, Myeroff L, Wang X, Gentry LE, Yang J, Liang J, Zborowska E, Markowitz S, Willson JKW, Brattain MG (1995) Demonstration that mutation of the type II transforming growth factor R receptor inactivates its tumor suppressor activity in replication error-positive colon carcinoma cells. J Biol Chem 270:22044

    Google Scholar 

  • Wang X-F, Lin HY, NG-Eaton E, Downward J, Lodish HF, Weinberg RA (1991) Expression cloning and characterization of the TGF-β type III receptor. Cell 67:797

    Google Scholar 

  • Weis-Garcia F, Massague J (1996) Complementation between kinase-defective and activation-defective TGF-β receptors reveals a novel form of receptor cooperativity essential for signaling. EMBO J 15:276

    Google Scholar 

  • Verhagen APM, Aalders TW, Ramackers FCS, Debruyne FMJ, Schalken JA (1988) Differential expression of keratins in the basal and luminal compartments of rat prostatic epithelium during degeneration and regeneration. Prostate 13:25

    Google Scholar 

  • Westin P, Brändström A, Damber J-E, Bergh A (1995) Castration plus oestrogen treatment induces but castration alone suppresses epithelial cell apoptosis in an androgen-sensitive rat prostatic adenocarcinoma. Br J Cancer 72:140

    Google Scholar 

  • Wilding G, Zugmeier G, Knabbe C, Flanders K, Gelmann E (1989) Differential effects of transforming growth factor β on human prostate cancer cells in vitro. Mol Cell Endocrinol 62:79

    Google Scholar 

  • Yamashita H, ten Dijke P, Franzén P, Miyazono K, Heldin C-A (1994) Formation of hetero-oligomeric complexes of type I and type II receptors for transforming growth factor-β. J Biol Chem 269:20172

    Google Scholar 

  • Zhao J, Buick RN (1993) Relationship of levels and kinetics of H-ras expression to transformed phenotype and loss of TGF-βI-mediated growth regulation in intestinal epithelial cells. Exp Cell Res 204:82

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wikström, P., Bergh, A. & Damber, J.E. Expression of transforming growth factor-β receptor type I and type II in rat ventral prostate and Dunning R3327 PAP adenocarcinoma in response to castration and oestrogen treatment. Urol. Res. 25, 103–111 (1997). https://doi.org/10.1007/BF01037924

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01037924

Keywords

Navigation